A Systematic Genomewide Linkage Study in 353 Sib Pairs with Schizophrenia

N. M. Williams; N. Norton; H. Williams; B. Ekholm; M. L. Hamshere; Y. Lindblom; K. V. Chowdari; A. G. Cardno; S. Zammit; L. A. Jones; K. C. Murphy; R. D. Sanders; G. McCarthy; M. Y. Gray; G. Jones; P. Holmans; V. Nimgaonkar; R. Adolfson; U. Ösby; L. Terenius; G. Sedvall; M. C. O'Donovan; M. J. Owen

doi:10.1086/380206

A Systematic Genomewide Linkage Study in 353 Sib Pairs with Schizophrenia

N. M. Williams
, N. Norton
, H. Williams
, B. Ekholm
, M. L. Hamshere
, Y. Lindblom
, K. V. Chowdari
, A. G. Cardno
, S. Zammit
, L. A. Jones
, K. C. Murphy
, R. D. Sanders
, G. McCarthy
, M. Y. Gray
, G. Jones
, P. Holmans
, V. Nimgaonkar
, R. Adolfson
, U. Ösby
, L. Terenius

G. Sedvall, M. C. O'Donovan, M. J. Owen

Cardiff University
Karolinska Institutet
Umeå University
University of Pittsburgh Medical Center

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

107 Citations (Scopus)

Abstract

We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at ∼10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P < .05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P < .02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

Original language	English
Pages (from-to)	1355-1367
Number of pages	13
Journal	American Journal of Human Genetics
Volume	73
Issue number	6
DOIs	https://doi.org/10.1086/380206
Publication status	Published - Dec 2003
Externally published	Yes

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Williams, N. M., Norton, N., Williams, H., Ekholm, B., Hamshere, M. L., Lindblom, Y., Chowdari, K. V., Cardno, A. G., Zammit, S., Jones, L. A., Murphy, K. C., Sanders, R. D., McCarthy, G., Gray, M. Y., Jones, G., Holmans, P., Nimgaonkar, V., Adolfson, R., Ösby, U., ... Owen, M. J. (2003). A Systematic Genomewide Linkage Study in 353 Sib Pairs with Schizophrenia. American Journal of Human Genetics, 73(6), 1355-1367. https://doi.org/10.1086/380206

@article{d1dd7a83b2f042d8a3cfb584c1f1cd0b,

title = "A Systematic Genomewide Linkage Study in 353 Sib Pairs with Schizophrenia",

abstract = "We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at ∼10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P < .05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P < .02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.",

author = "Williams, \{N. M.\} and N. Norton and H. Williams and B. Ekholm and Hamshere, \{M. L.\} and Y. Lindblom and Chowdari, \{K. V.\} and Cardno, \{A. G.\} and S. Zammit and Jones, \{L. A.\} and Murphy, \{K. C.\} and Sanders, \{R. D.\} and G. McCarthy and Gray, \{M. Y.\} and G. Jones and P. Holmans and V. Nimgaonkar and R. Adolfson and U. {\"O}sby and L. Terenius and G. Sedvall and O'Donovan, \{M. C.\} and Owen, \{M. J.\}",

year = "2003",

month = dec,

doi = "10.1086/380206",

language = "English",

volume = "73",

pages = "1355--1367",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "6",

}

Williams, NM, Norton, N, Williams, H, Ekholm, B, Hamshere, ML, Lindblom, Y, Chowdari, KV, Cardno, AG, Zammit, S, Jones, LA, Murphy, KC, Sanders, RD, McCarthy, G, Gray, MY, Jones, G, Holmans, P, Nimgaonkar, V, Adolfson, R, Ösby, U, Terenius, L, Sedvall, G, O'Donovan, MC & Owen, MJ 2003, 'A Systematic Genomewide Linkage Study in 353 Sib Pairs with Schizophrenia', American Journal of Human Genetics, vol. 73, no. 6, pp. 1355-1367. https://doi.org/10.1086/380206

TY - JOUR

T1 - A Systematic Genomewide Linkage Study in 353 Sib Pairs with Schizophrenia

AU - Williams, N. M.

AU - Norton, N.

AU - Williams, H.

AU - Ekholm, B.

AU - Hamshere, M. L.

AU - Lindblom, Y.

AU - Chowdari, K. V.

AU - Cardno, A. G.

AU - Zammit, S.

AU - Jones, L. A.

AU - Murphy, K. C.

AU - Sanders, R. D.

AU - McCarthy, G.

AU - Gray, M. Y.

AU - Jones, G.

AU - Holmans, P.

AU - Nimgaonkar, V.

AU - Adolfson, R.

AU - Ösby, U.

AU - Terenius, L.

AU - Sedvall, G.

AU - O'Donovan, M. C.

AU - Owen, M. J.

PY - 2003/12

Y1 - 2003/12

N2 - We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at ∼10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P < .05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P < .02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

AB - We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at ∼10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P < .05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P < .02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

UR - https://www.scopus.com/pages/publications/9144220855

U2 - 10.1086/380206

DO - 10.1086/380206

M3 - Article

SN - 0002-9297

VL - 73

SP - 1355

EP - 1367

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

A Systematic Genomewide Linkage Study in 353 Sib Pairs with Schizophrenia

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